Studies will be conducted on hormonal and neural mechanisms which contribute to the etiology or exacerbation of hypertension and its sequelae. The focus of several units will be the renin-angiotensin system and studies will be conducted in the following areas: role of angiotensinogen in central mechanisms of blood pressure control and in hypertensive animals; relationship of adrenal corticosterone and mineralcorticoids to central angiotensin system; the role of angiotensin and neural pathways in controlling glomerular filtration and renovascular resistance; the dissociation of renin release and renal artery blood flow in the diving sea mammal and the role of the angiotensin system in salt and fresh water fishes. Changes in the mechanical state of arteries will be measured in vivo in hypertensive swine and correlated with alterations in hormonal state. The blood vessel in hypertension will be studied by several units using different approaches: studies of adrenergic receptor responsiveness will be quantified using receptor identification probes and the interaction between adrenergic and cholinergic receptors in blood vessels will be assessed. Prostaglandin biosynthetic pathways in the microvessels of the brain, retina, heart and kidney will be defined in normotensive and hypertensive animals which will permit the assessment of the role of prostaglandins in hypertension-mediated target organ damage. Central pathways important in blood pressure control will be defined both anatomically and by neurophysiologic methods in hypertensive animals, primates and man. The relationship of the kallikrein-kinin system to the state of sympathetic activity in man will be defined in ongoing clinical studies and the role of chronic antihypertensive therapy on these systems will be demonstrated. Ongoing clinical studies will overlap animal experimentation and the goal of all units will be to extend their findings in animals into unique clinical investigations in man. The mechanisms inherent in SCOR will make this possible during the tenure of the grant.
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